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Tumor Cells Modified with Newcastle Disease Virus Expressing IL-24 as a Cancer Vaccine
Molecular Therapy: Oncology ( IF 5.7 ) Pub Date : 2019-06-12 , DOI: 10.1016/j.omto.2019.06.001
Xiaojing Xu , Cheng Yi , Xiaoqin Yang , Jianwei Xu , Qing Sun , Yonghao Liu , Lixiang Zhao

Interleukin-24 (IL-24) is a promising agent for cancer immunotherapy that induces apoptosis of tumor cells and enhances T cell activation and function. In order to improve the antitumor activity induced by Newcastle disease virus (NDV)-modified tumor vaccine, we generated a recombinant NDV expressing IL-24 using reverse genetics. Irradiated tumor cells infected with LX/IL-24 showed stable IL-24 expression. The cytotoxicity assay showed that LX/IL-24-infected murine melanoma cells significantly enhanced the antitumor immune response in vitro. Then, the antitumor effects of virus-infected tumor cells were examined in the murine tumor models. LX/IL-24-infected tumor cells exhibited strong antitumor effects both in prophylaxis and therapeutic models. LX/IL-24-infected tumor cells increased infiltration of CD4+ T cells and CD8+ T cells in tumor sites, and the antitumor activity of the tumor vaccine modified with LX/IL-24 was dependent on CD8+ T cells. Taken together, our data well illustrates that LX/IL-24-modified tumor cells are a promising agent for cancer immunotherapy.



中文翻译:

用表达IL-24作为癌症疫苗的新城疫病毒修饰的肿瘤细胞

白介素24(IL-24)是一种有前途的癌症免疫治疗剂,可诱导肿瘤细胞凋亡并增强T细胞活化和功能。为了提高新城疫病毒(NDV)修饰的肿瘤疫苗诱导的抗肿瘤活性,我们使用反向遗传学产生了表达IL-24的重组N​​DV。用LX / IL-24感染的辐射肿瘤细胞显示稳定的IL-24表达。细胞毒性试验表明,LX / IL-24感染的鼠黑色素瘤细胞显着增强了体外的抗肿瘤免疫反应。然后,在鼠肿瘤模型中检查了病毒感染的肿瘤细胞的抗肿瘤作用。LX / IL-24感染的肿瘤细胞在预防和治疗模型中均表现出强大的抗肿瘤作用。LX / IL-24感染的肿瘤细胞增加了CD4的浸润+ T细胞和CD8 + T细胞在肿瘤部位,经LX / IL-24修饰的肿瘤疫苗的抗肿瘤活性取决于CD8 + T细胞。两者合计,我们的数据很好地说明了LX / IL-24修饰的肿瘤细胞是用于癌症免疫治疗的有前途的药物。

更新日期:2019-06-12
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